Publications by authors named "Mani D"

Article Synopsis
  • The study presents an optimized workflow for analyzing formalin-fixed, paraffin-embedded (FFPE) patient tissues to uncover molecular insights linked to clinical outcomes, utilizing advanced techniques like Adaptive Focused Acoustics (AFA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  • The method allows for the analysis of up to 96 samples, identifying between 8,000-10,000 unique proteins with a high level of quantitative accuracy (<20% median CVs).
  • Applied to lung adenocarcinoma FFPE blocks, the workflow demonstrates superior deep proteome coverage and efficiency, significantly contributing to biomarker discovery and proteomic research in archived samples.
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The emerging field of induced proximity therapeutics, which involves designing molecules to bring together an effector and target protein-typically to induce target degradation-is rapidly advancing. However, its progress is constrained by the lack of scalable and unbiased tools to explore effector-target protein interactions. We combine pooled endogenous gene tagging using a ligand-binding domain with generic small-molecule-based recruitment to screen for induction of protein proximity.

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Over more than a decade, lead halide perovskites (LHPs) have been popular as a next-generation semiconductor for optoelectronics. Later, all-inorganic CsPbX (X = Cl, Br, and I) nanocrystals (NCs) were synthesized supersaturated recrystallization (SR) at room temperature (RT). However, compared to the hot injection (HI) method, the formation mechanism of NCs SR-RT has not been well studied.

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Breast cancer is the most common cancer in women worldwide, and its treatment usually involves a combination of many medical procedures, including surgery, chemotherapy, radiotherapy, and hormonal therapy. One of the detrimental effects on physical function is reduced upper limb muscle strength. This study aimed to evaluate upper body strength intra-day and inter-day (test-retest) reliability using the handgrip strength test (HGS) and the bilateral isometric bench press (BIBP) and the test-retest reliability of the one repetition maximum on the bench press (BP-1RM) in breast cancer survivors (BCS).

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In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear.

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Article Synopsis
  • Despite extensive research on genomic changes in glioblastoma, the survival rate remains under 5% after five years.
  • This study aims to broaden the understanding of high-grade glioma by combining various biological analyses (proteomics, metabolomics, etc.) to identify complex regulatory mechanisms involved in tumor growth and progression.
  • Results from analysis of 228 tumors indicate significant variability in early-stage changes, but they converge on common outcomes affecting protein interactions and modifications, highlighting PTPN11's crucial role in high-grade gliomas.
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The recent technological and computational advances in mass spectrometry-based single-cell proteomics have pushed the boundaries of sensitivity and throughput. However, reproducible quantification of thousands of proteins within a single cell remains challenging. To address some of those limitations, we present a dedicated sample preparation chip, the proteoCHIP EVO 96 that directly interfaces with the Evosep One.

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Hydrogen-bonding and carbon-bonding interactions are widespread in nature. We studied the cooperativity between these interactions in 42 trimeric complexes ZY···CHCN/CHNC···HX, where ZY molecules are HO, HS, HF, HCl, HBr, NH, and HCO, and HX molecules are HF, HCl, and HBr. Acetonitrile (CHCN) and isoacetonitrile (CHNC) act as hydrogen bond acceptors as well as carbon bond donors in these trimers.

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This study examined the influence of fireworks on atmospheric aerosols over the Southern Indian city of Hyderabad during festival of Diwali using mass closure, stable carbon isotopes and the EPA-PMF model. Identification of chemical species in day and night time aerosol samples for 2019 and 2020 Diwali weeks showed increased concentrations of NH, NO, SO, K, organic carbon (OC), Ba, Pb and Li, which were considered as tracers for fireworks. PM source apportionment was done using inorganic (trace elements, major ions) and carbonaceous (organic and elemental carbon; OC & EC) constituents, along with stable isotopic compositions of TC and EC.

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Leone et al. reveal that Pol III transcription complexes recruit a chaperone, HSP70, to execute cotranscriptional cleavage of precursor tRNA. HSP70 binds to the polymerase and translocates to nascent precursor tRNA and then tRNA.

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Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%-20% cancer cases have demonstrated durable responses from immune checkpoint blockade. To enhance the efficacy of immunotherapies, combination therapies suppressing multiple immune evasion mechanisms are increasingly contemplated. To better understand immune cell surveillance and diverse immune evasion responses in tumor tissues, we comprehensively characterized the immune landscape of more than 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic data.

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Mass spectrometry (MS)-based single-cell proteomics (SCP) has gained massive attention as a viable complement to other single cell approaches. The rapid technological and computational advances in the field have pushed the boundaries of sensitivity and throughput. However, reproducible quantification of thousands of proteins within a single cell at reasonable proteome depth to characterize biological phenomena remains a challenge.

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Background: Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed.

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Article Synopsis
  • - The study investigates how precursor tRNAs, which are initially transcribed with extra sequences, are processed by specific enzymes called ribonucleases, particularly focusing on RNA polymerase III complexes.
  • - It demonstrates that RNase P, which is part of these complexes, cleaves precursor tRNA and also degrades the unnecessary leader sequence, with the protein subunit Rpp14 playing a key role in this degradation process.
  • - It highlights that reducing Rpp14 levels through RNA interference significantly disrupts the cleavage of precursor tRNAs, indicating that RNase P is essential for the proper maturation of tRNAs by managing various processing enzymes.
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The field of induced proximity therapeutics is in its ascendancy but is limited by a lack of scalable tools to systematically explore effector-target protein pairs in an unbiased manner. Here, we combined Scalable POoled Targeting with a LIgandable Tag at Endogenous Sites (SPOTLITES) for the high-throughput tagging of endogenous proteins, with generic small molecule-based protein recruitment to screen for novel proximity-based effectors. We apply this methodology in two orthogonal screens for targeted protein degradation: the first using fluorescence to monitor target protein levels directly, and the second using a cellular growth phenotype that depends on the degradation of an essential protein.

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The phase change of all-inorganic cesium lead halide (CsPbI) thin film from yellow δ-phase to black γ-/α-phase has been a topic of interest in the perovskite optoelectronics field. Here, the main focus is how to secure a black perovskite phase by avoiding a yellow one. In this work, we fabricated a self-doped CsPbI thin film by incorporating an excess cesium iodide (CsI) into the perovskite precursor solution.

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We introduce a pioneering approach that integrates pathology imaging with transcriptomics and proteomics to identify predictive histology features associated with critical clinical outcomes in cancer. We utilize 2,755 H&E-stained histopathological slides from 657 patients across 6 cancer types from CPTAC. Our models effectively recapitulate distinctions readily made by human pathologists: tumor vs.

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Article Synopsis
  • DNA methylation is crucial for maintaining cellular identity, but it's often disrupted in tumors and linked with other genetic changes.
  • Researchers analyzed 687 tumors and adjacent normal tissues across various organs to create a Pan-Cancer catalog, highlighting specific methylation patterns.
  • They discovered that certain methylation changes are associated with cancer characteristics, such as hypomethylated FGFR2 in endometrial cancer and hypermethylated STAT5A leading to immune suppression in squamous tumors, revealing the importance of methylation in tumor behavior.
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Article Synopsis
  • Post-translational modifications (PTMs) significantly influence cell signaling and physiology in both healthy and cancerous cells, with recent advancements in mass spectrometry allowing for precise analysis of these modifications.* -
  • This study utilizes the largest dataset of proteogenomics from 1,110 cancer patients to uncover widespread patterns of protein changes, particularly focusing on acetylation and phosphorylation across 11 cancer types.* -
  • Findings show that specific cancer types exhibit unique PTM-related alterations linked to processes like DNA repair, immune response, kinase activity, and histone regulation, suggesting new potential therapeutic targets.*
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In this study, heterostructured g-CN/Ag-TiO nanocomposites were successfully fabricated using an easily accessible hydrothermal route. Various analytical tools were employed to investigate the surface morphology, crystal structure, specific surface area, and optical properties of as-synthesized samples. XRD and TEM characterization results provided evidence of the successful fabrication of the ternary g-CN/Ag-TiO heterostructured nanocomposite.

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We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity.

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Room temperature (RT) synthesis of the ternary cesium lead bromide CsPbBr quantum dots with oleic acid and oleylamine ligands was developed by Zeng and coworkers in 2016. In their works, the supersaturated recrystallization (SR) was adopted as a processing method without requiring inert gas and high-temperature injection. However, the oleic acid ligand for haloplumbate is known to be relatively unstable.

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The field of induced proximity therapeutics is in its ascendancy but is limited by a lack of scalable tools to systematically explore effector-target protein pairs in an unbiased manner. Here, we combined Scalable POoled Targeting with a LIgandable Tag at Endogenous Sites (SPOTLITES) for the high-throughput tagging of endogenous proteins, with generic small molecule-based protein recruitment to screen for novel proximity-based effectors. We apply this methodology in two orthogonal screens for targeted protein degradation: the first using fluorescence to monitor target protein levels directly, and the second using a cellular growth phenotype that depends on the degradation of an essential protein.

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Therapeutic drug monitoring (TDM) is recommended for medications with high inter-individual variability, narrow therapeutic index drugs, possible drug-drug interactions, drug toxicity, and subtherapeutic concentrations, as well as to assess noncompliance. The area under the plasma concentration-time curve (AUC) is a significant pharmacokinetic parameter since it calculates the drug's total systematic exposure in the body. However, multiple blood samples from the patient are required to calculate the area under the curve, which is inconvenient for both the patient and the healthcare professional.

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Synaptic dysfunction is implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BP). We use quantitative mass spectrometry to carry out deep, unbiased proteomic profiling of synapses purified from the dorsolateral prefrontal cortex of 35 cases of SCZ, 35 cases of BP, and 35 controls. Compared with controls, SCZ and BP synapses show substantial and similar proteomic alterations.

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